Role of complement in neurologic autoimmunities: Why need to target complement activation for effective immunotherapy

Area of Science:

• Immunology
• Neuroscience

Background:

• The complement system is crucial for innate and adaptive immunity, protecting against pathogens while clearing damaged cells.
• Its complexity involves multiple activation pathways (classical, lectin, alternative) converging on C3 activation.
• The alternative pathway's amplification loop is central to complement's effector functions and can contribute to autoimmune pathology.

Purpose of the Study:

• To review the role of the complement system in autoimmune and autoinflammatory conditions, particularly neurologic disorders.
• To highlight the therapeutic potential of complement-targeted immunotherapies for autoimmune neurologic diseases.
• To discuss emerging anticomplement biologics in clinical trials.

Main Methods:

• Literature review of complement pathways and their role in autoimmunity.
• Analysis of complement's involvement in autoimmune neurologic disorders.
• Overview of current and developing complement-targeted therapies.

Main Results:

• Dysregulated complement function, particularly the alternative pathway's amplification loop, drives autoimmune and neurologic conditions.
• Complement activation leads to inflammation and tissue damage, exacerbating autoimmune neurologic disorders.
• Targeting specific complement proteins offers a promising therapeutic strategy.

Conclusions:

• Complement-targeted immunotherapies, including novel biologics, are effective in suppressing neurologic autoimmunities.
• Emerging anticomplement agents show therapeutic potential for autoimmune neurologic conditions resistant to current treatments.
• Further research and clinical trials are essential for optimizing complement-based therapies.